Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women

• Register: ClinicalTrials.gov
• Last refreshed on: 16 March 2021
• Main ID: NCT02568215
• Date of registration: 01/10/2015
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women
• Scientific title: A Phase 2b Study to Evaluate the Safety and Efficacy of VRC01 Broadly Neutralizing Monoclonal Antibody in Reducing Acquisition of HIV-1 Infection in Women in Sub-Saharan Africa
• Date of first enrolment: May 2016
• Target sample size: 1924
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02568215
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania, United States, Zimbabwe

Contacts

• Name: Lawrence Corey
• Affiliation: HVTN; FHCRC

• Name: Myron Cohen
• Affiliation: HPTN; University of North Carolina

Key inclusion & exclusion criteria

Inclusion Criteria:

General and Demographic Criteria

- Age of 18 to 50 years

- Access to a participating clinical research site (CRS) and willingness to be followed
for the planned duration of the study

- Ability and willingness to provide informed consent

- Assessment of understanding: volunteer demonstrates understanding of this study and
completes a questionnaire prior to first infusion with verbal demonstration of
understanding of all questionnaire items answered incorrectly

- Agrees not to enroll in another study of an investigational research agent for the
duration of the participant's trial participation

- Good general health as shown by medical history, physical exam, and screening
laboratory tests

HIV-Related Criteria

- Willingness to receive HIV test results

- Willingness to discuss HIV infection risks and amenable to HIV risk reduction
counseling

- Persons born Female (assigned female sex at birth) and identifying as a female, who,
in the 6 months prior to randomization, has had vaginal and/or anal intercourse with a
male partner

- All volunteers who have been in a monogamous relationship with an HIV-1 seronegative
partner for greater than 1 year are excluded.

Laboratory Inclusion Values+

Hematology

- Hemoglobin (Hgb) greater than or equal to 10.5 g/dL for volunteers who were born
female, greater than or equal to 13.0 g/dL for volunteers who were born male

- Platelets greater than or equal to 100,000 cells/mm^3

Chemistry

- Alanine aminotransferase (ALT) less than 2.5 times the institutional upper limit of
normal and creatinine less than or equal to 1.25 times the institutional upper limit
of normal

Virology

- HIV uninfected, as defined in the study specific procedures (SSP), within 30 days
prior to enrollment

Urine

- Negative, trace, or 1+ urine protein by dipstick

Reproductive Status

- Volunteers capable of becoming pregnant: negative serum or urine beta human chorionic
gonadotropin (ß-HCG) pregnancy test performed at the screening visit and prior to
infusion on the day of initial infusion. Persons who are NOT capable of becoming
pregnant due to having undergone total hysterectomy or bilateral oophorectomy
(verified by medical records) are not required to undergo pregnancy testing.

- Reproductive status: A volunteer who is capable of becoming pregnant must agree to
consistently use effective contraception (see the protocol and SSP for more
information) for sexual activity that could lead to pregnancy from at least 21 days
prior to enrollment through the last required protocol clinic visit.

- Volunteers capable of becoming pregnant must also agree not to seek pregnancy through
alternative methods, such as artificial insemination or in vitro fertilization until
after the last required protocol clinic visit

Exclusion Criteria:

General

- Investigational research agents received within 30 days before first infusion

- Body mass index (BMI) greater than or equal to 40

- Pregnant or breastfeeding

- Any reactive, indeterminate, or positive HIV test, even if subsequent testing
indicates that the individual is not HIV infected.

Monoclonal antibodies and vaccines

- Previous receipt of humanized or human monoclonal antibodies (mAbs), whether licensed
or investigational

- HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received
control/placebo in an HIV vaccine trial, the HVTN 703/HPTN 081 Protocol Safety Review
Team (PSRT) will determine eligibility on a case-by-case basis.

Immune System

- Serious adverse reactions to VRC01 formulation components such as sodium citrate,
sodium chloride, and L-arginine hydrochloride, including history of anaphylaxis and
related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal
pain.

- Autoimmune disease, including Type I diabetes mellitus (Not excluded from
participation: Volunteer with mild, stable and uncomplicated autoimmune disease that
does not require consistent immunosuppressive medication and that, in the judgment of
the site investigator, is likely not subject to exacerbation and likely not to
complicate reactogenicity and adverse event (AE) assessments)

- Immunodeficiency syndrome

Clinically significant medical conditions

- Clinically significant medical condition, physical examination findings, clinically
significant abnormal laboratory results, or past medical history with clinically
significant implications for current health. A clinically significant condition or
process includes but is not limited to:

- Any contraindication to repeated infusions or blood draws, including inability to
establish venous access;

- A condition that requires active medical intervention or monitoring to avert
grave danger to the volunteer's health or well-being during the study period; or

- A condition or process for which signs or symptoms could be confused with
reactions to VRC01.

- Any medical, psychiatric, occupational, or other condition that, in the judgment of
the investigator, would interfere with, or serve as a contraindication to, protocol
adherence, assessment of safety or infusion reactions, or a volunteer's ability to
give informed consent

- Psychiatric condition that precludes compliance with the protocol. Specifically
excluded are persons with psychoses within the past 3 years, ongoing risk for suicide,
or history of suicide attempt or gesture within the past 3 years.

- Asthma, other than mild, well-controlled asthma

- Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or
platelet disorder requiring special precautions)

- Malignancy (Not excluded from participation: Volunteer who has had malignancy excised
surgically and who, in the investigator's estimation, has a reasonable assurance of
sustained cure. or who is unlikely to experience recurrence of malignancy during the
period of the study)

- Seizure disorder: History of seizure(s) within past three years. Also exclude if
volunteer has used medications in order to prevent or treat seizure(s) at any time
within the past 3 years.

- History of hereditary angioedema, acquired angioedema, or idiopathic angioedema

- History


Age minimum: 18 Years
Age maximum: 50 Years
Gender: Female

Health Condition(s) or Problem(s) studied

HIV Infections

Intervention(s)

Biological: VRC01

Biological: Placebo for VRC01

Primary Outcome(s)

Rates of participant discontinuation from the study [Time Frame: Measured through Week 92]

Number of participants with adverse events (AEs) [Time Frame: Measured through Week 92]

Number of participants with local and systemic reactogenicity signs and symptoms [Time Frame: Measured through Week 92]

Number of participants with severe adverse events (SAEs) [Time Frame: Measured through Week 92]

Documented HIV-1 infection by the Week 80 study visit [Time Frame: Measured through Week 80]

Secondary Outcome(s)

Serum concentration of VRC01 in participants assigned to receive the mAb (ELISA, neutralizing assay) [Time Frame: Measured through Week 92]

Sequences of breakthrough HIV infections from the earliest available HIV-positive plasma samples [Time Frame: Measured through Week 92]

Serum mAb effector functions to HIV-1 Envs representing variability of the VRC01 antibody footprint [Time Frame: Measured through Week 92]

VRC01 neutralization-sensitivity of, and effector function against, HIV strains from infected trial participants from the earliest available post-HIV-infection serum samples [Time Frame: Measured through Week 92]

Secondary ID(s)

HVTN 703/HPTN 081

12045

Source(s) of Monetary Support

Please refer to primary and secondary sponsors